This Program Grant serves as the animal investigative arm of this integrated program. The studies in this program, therefore, are directed toward description of fundamental biologic processes, including cellular and subcellular enzyme kinetics, action potentials, contractility and segment performance, regional and collateral perfusion. Particular emphasis is also placed upon development and application of new technology for these studies. Most projects in the program include a multidisciplinary approach involving mechanics, hemodynamic and flow measurements, metabolism, electrophysiology, pharmacology and biochemistry. Dog studies of regional ischemia employ epicardial strain gauges and length gauges and include measurements of coronary sinus blood flow by the continuous thermodilution techniques. In vitro studies of pharmacology and electrophysiology utilize isolated cat and canine heart muscle. In summary, it is anticipated that our continued efforts will provide a more detailed description of the physiologic consequences of cardiac ischemia, and will thus provide more rationale guidelines for the therapy of patients with acute and chronic coronary artery disease. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application. BIBLIOGRAPHIC REFERENCE: Swan HJC: Impedance reduction by pharmacological and mechanical means in the management of severe power failure of the heart. In Cardiovascular Problems (Edited by Henry I. Russek), University Park Press, 1976, Baltimore. Swan HJC; Duration of hospitalization in "uncomplicated completed acute myocardial infarction" -- An Ad Hoc Committee Review. Am J Cardiol 37:413, 1976.